Thrombo-Inflammatory Prognostic Scores Improve BISAP-Based Risk Stratification in Acute Pancreatitis Patients: A Retrospective Cohort Study

Figures & data

Table 1 Basic Characteristics of the Derivation Group and the Validation Group

Variable	Derivation Group (n=220)	Validation Group (n=220)	P-value
Baseline
Age (years)	48.42 (±14.33)	48.54 (±15.46)	0.936
Male, n (%)	130 (59.1%)	137 (62.3%)	0.494
BMI	25.50 (23.02–27.86)	25.75 (23.38–27.68)	0.910
Etiology, n (%)			0.384
Gallstone	75 (34.1%)	79 (35.9%)
Hyperlipemia	82 (37.3%)	81 (36.8%)
Alcohol abuse	21 (9.5%)	29 (13.2%)
Unknown	42 (19.1%)	31 (14.1%)
PH	7.44 (7.40–7.47)	7.43 (7.39–7.47)	0.441
WBC (10^9/L)	13.12 (10.16–16.89)	13.38 (9.43–17.24)	0.984
PLT (10^9/L)	160.00 (119.00–205.50)	162.50 (126.50–215.50)	0.182
Hb (g/L)	131.63 (±28.89)	132.45 (±27.75)	0.762
HCT (%)	0.39 (0.34–0.44)	0.39 (0.34–0.43)	0.755
TBIL (umol/L)	19.75 (13.30–32.53)	20.10 (12.33–32.25)	0.942
ALT (IU/L)	31.00 (16.25–72.75)	30.50 (18.25–58.75)	0.717
AST (IU/L)	33.50 (21.00–71.50)	34.00 (22.00–71.00)	0.798
Albumin (g/L)	35.70 (31.43–41.10)	37.05 (31.55–41.60)	0.212
Cr (umol/L)	66.00 (52.25–88.75)	68.00 (55.25–91.75)	0.434
BUN (mg/dL)	4.72 (3.37–6.52)	4.96 (3.54–7.37)	0.244
CHOL (mmol/L)	3.94 (2.97–5.75)	4.20 (3.24–5.78)	0.143
TG (mmol/L)	1.89 (1.06–4.90)	2.39 (1.21–6.03)	0.152
HDL-C (mmol/L)	0.83 (0.54–1.19)	0.85 (0.49–1.15)	0.904
LDL-C (mmol/L)	1.38 (0.76–2.24)	1.47 (0.72–2.31)	0.649
LIP (U/L)	266.50 (99.00–832.00)	208.00 (80.25–791.25)	0.298
AMY (U/L)	236.50 (93.00–657.75)	179.50 (71.00–627.75)	0.360
Ca (mmol/L)	2.07 (1.87–2.21)	2.09 (1.90–2.25)	0.412
PT (s)	13.00 (12.00–14.20)	12.75 (12.00–14.10)	0.337
APTT (s)	30.65 (27.58–34.98)	30.60 (28.00–35.08)	0.989
CRP (mg/L)	163.00 (85.48–267.00)	158.50 (76.53–266.75)	0.635
PCT (ng/mL)	0.41 (0.14–1.23)	0.47 (0.17–1.88)	0.176
IL-6 (pg/mL)	91.38 (35.67–183.83)	78.34 (30.86–168.50)	0.357
LAC (mmol/L)	1.60 (1.20–2.28)	1.50 (1.30–2.20)	0.416
Severity			0.708
MAP, n (%)	31 (14.1%)	27 (12.3%)
MSAP, n (%)	61 (27.7%)	68 (30.9%)
SAP, n (%)	128 (58.2%)	125 (56.8%)
Scores
APACHE II	7 (4–10)	7 (5–10)	0.288
TIPS	1 (0–1)	1 (0–1)	0.053
BISAP	2 (1–2)	2 (1–3)	0.250
Endpoint event
Death, n (%)	14 (6.4%)	13 (5.9%)	0.843
AICU, n (%)	37 (16.8%)	46 (20.9%)	0.273
MV, n (%)	65 (29.5%)	69 (31.4%)	0.679

Abbreviations: BMI, body mass index; PH, potential of hydrogen; WBC, white blood cell; PLT, platelets; HB, hemoglobin; HCT, hematocrit; TBIL, total bilirubin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; Cr, creatinine; BUN, blood urea nitrogen; CHOL, cholesterol; TG, triglyceride; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; LIP, lipase; AMY, amylase; Ca, calcium; PT, prothrombin time; APTT, activated partial thromboplastin time; CRP, C-reactive protein; PCT, procalcitonin; IL-6, interleukin-6; LAC, lactate; MAP, mild acute pancreatitis; MSAP, moderately severe acute pancreatitis; SAP, severe acute pancreatitis; APACHE II, acute physiology and chronic health evaluation scoring system; TIPS, thrombo-inflammatory prognostic score; BISAP, bedside index for severity in AP; AICU, admission to intensive care unit; MV, mechanical ventilation.

Table 2 Characteristics of Patients in the Derivation Group

Variable	Survial (n = 206)	Death (n = 14)	P-value
Baseline variables
Age (years)	47.96 (±14.18)	55.29 (±15.31)	0.103
Male, n (%)	124 (60.2%)	6 (42.9%)	0.202
BMI	25.60 (±4.00)	25.11 (±5.43)	0.661
Etiology, n (%)			0.140
Gallstone	72 (35.0%)	2 (14.3%)
Hyperlipemia	75 (36.4%)	4 (28.6%)
Alcohol abuse	17 (8.3%)	2 (14.3%)
Unknown	42 (20.4%)	6 (42.9%)
PH	7.44 (7.07–7.47)	7.37 (7.33–7.46)	0.077
WBC (10^9/L)	13.06 (10.15–16.65)	16.65 (10.71–19.93)	0.115
PLT (10^9/L)	159.00 (119.00–201.00)	179.50 (85.50–224.25)	0.679
Hb (g/L)	133.37 (±27.66)	106.07 (±35.27)	0.001
HCT (%)	39.17 (±6.89)	32.79 (±9.85)	0.001
TBIL (μmol/L)	20.35 (13.20–32.83)	15.90 (14.18–18.40)	0.248
ALT (IU/L)	31.00 (17.00–74.00)	30.00 (14.25–55.25)	0.653
AST (IU/L)	32.25 (21.00–67.75)	49.50 (22.75–77.50)	0.442
Albumin (g/L)	36.00 (31.40–41.40)	34.20 (31.60–36.50)	0.191
Cr (μmol/L)	66.00 (52.00–87.00)	104.00 (53.25–257.50)	0.102
BUN (mg/dL)	4.64 (3.33–6.32)	12.57 (4.01–17.40)	0.003
CHOL (mmol/L)	3.99 (3.08–6.01)	2.30 (1.89–3.88)	<0.001
TG (mmol/L)	2.09 (1.06–5.21)	1.52 (0.80–2.05)	0.086
HDL-C (mmol/L)	0.85 (0.54–1.19)	0.65 (0.36–0.99)	0.111
LDL-C (mmol/L)	1.38 (0.81–2.24)	1.00 (0.44–1.96)	0.307
LIP (IU/L)	275.00 (100.50–826.00)	158.50 (32.25–1113.25)	0.293
AMY (IU/L)	245.00 (96.00–666.50)	81.50 (38.75–809.50)	0.176
Ca (mmol/L)	2.07 (1.89–2.21)	2.07 (1.79–2.21)	0.929
PT (s)	12.90 (11.98–13.90)	14.95 (14.33–17.78)	<0.001
APTT (s)	30.50 (27.30–34.38)	35.30 (30.90–45.10)	0.004
CRP (mg/L)	165.50 (83.63–267.25)	122.50 (86.43–218.00)	0.773
PCT (ng/mL)	0.41 (0.14–1.17)	0.72 (0.18–4.27)	0.401
IL-6 (pg/mL)	87.93 (30.14–168.90)	133.25 (87.37–266.50)	0.035
LAC (mmol/L)	1.50 (1.20–2.20)	2.00 (1.50–2.55)	0.097
Severity			0.024
MAP, n (%)	31 (15.0%)	0 (0.0%)
MSAP, n (%)	60 (29.1%)	1 (7.1%)
SAP, n (%)	115 (55.8%)	13 (92.9%)
Scores
APACHE II	6 (4–9)	11 (10–14)	<0.001
BISAP	2 (1–2)	3 (2–4)	<0.001
TIPS	1 (0–1)	2 (2–2)	<0.001

Abbreviations: BMI, body mass index; PH, potential of hydrogen; WBC, white blood cell; PLT, platelets; HB, hemoglobin; HCT, hematocrit; TBIL, total bilirubin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; Cr, creatinine; BUN, blood urea nitrogen; CHOL, cholesterol; TG, triglyceride; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; LIP, lipase; AMY, amylase; Ca, calcium; PT, prothrombin time; APTT, activated partial thromboplastin time; CRP, C-reactive protein; PCT, procalcitonin; IL-6, interleukin-6; LAC, lactate; MAP, mild acute pancreatitis; MSAP, moderately severe acute pancreatitis; SAP, severe acute pancreatitis; APACHE II, acute physiology and chronic health evaluation scoring system; TIPS, thrombo-inflammatory prognostic score; BISAP, bedside index for severity in AP.

Figure 1 (A) Comparison of BISAP score between death group and survival group; (B) comparison of TIPS score between death group and survival group; (C) comparison of BISAP score between AICU group and Non-AICU group; (D) comparison of TIPS score between AICU group and Non-AICU group; (E) comparison of BISAP score between MV group and Non-MV group; (F) comparison of TIPS score MV group and Non-MV group. All data are median (IQR) and compared using the Mann–Whitney U-test. **P < 0.05, ***P < 0.001.

Abbreviations: TIPS, thrombo-inflammatory prognostic score; BISAP, bedside index for severity in AP; AICU, admission to intensive care unit; MV, mechanical ventilation.

Table 3 Correlation Analysis

Scores	28-Day Mortality		AICU		MV
	r	P	r	P	r	P
BISAP	0.336	<0.001	0.435	<0.001	0.385	<0.001
TIPS	0.328	<0.001	0.194	0.004	0.241	<0.001
T-BISAP	0.389	<0.001	0.436	<0.001	0.395	<0.001

Table 4 Univariable and Multivariable Logistic Regression Analyses of the T-BISAP Associated with the Clinical Adverse Outcomes in Patients with AP

Clinical Outcomes	T-BISAP
	OR	95% CI		P-value
		Lower	Upper
28-day mortality
Unadjusted	2.719	1.756	4.211	<0.001
Adjusted^a	2.894	1.705	4.914	<0.001
AICU
Unadjusted	2.718	1.906	3.875	<0.001
Adjusted^a	3.040	2.022	4.570	<0.001
MV
Unadjusted	2.720	1.875	3.945	<0.001
Adjusted^a	3.018	1.989	4.579	<0.001

Note: ^aRisk factors adjustment included age, gender, BMI, etiology.

Abbreviations: AICU, admission to intensive care unit; MV, mechanical ventilation; OR, odds ratio; CI, confidence interval.

Table 5 ROC Curve Analysis of Predicting Prognosis of Patients with AP in the Derivation Group

Scores	AUC	95% CI	P-value	Sensitivity%	Specificity%	+LR	-LR
BISAP	0.809	0.751–0.859	<0.001	57.14	84.47	3.68	0.51
T-BISAP	0.903	0.856–0.939	<0.001	85.71	83.50	5.19	0.17

Abbreviations: BISAP, bedside index for severity in AP; AUC, area under the curve; CI, confidence interval; LR, likelihood ratio.

Figure 2 ROC curves analysis for predicting 28-day mortality.

Figure 3 (A) AUCs of the prediction of 28-day mortality; (B) AUCs of the prediction of AICU; (C) AUCs of the prediction of MV.

Abbreviations: T-BISAP, combination of thrombo-inflammatory prognostic score (TIPS) and BISAP; BISAP, bedside index for severity in acute pancreatitis; APACHE II, acute physiology and chronic health evaluation II.

Figure 4 Decision-curve analysis (DCA) for predicting acute pancreatitis 28-day mortality. Decision curve analysis for the T-BISAP and BISAP. The x-axis shows the threshold probability, and the y-axis measures the net benefit. The red line represents the T-BISAP. The green line represents the BISAP. The thin gray line indicates the hypothesis that all patients died within 28 days. The bold black line indicates the hypothesis that no patient died within 28 days.

Abbreviations: BISAP, bedside index for severity in acute pancreatitis; T-BISAP, combination of thrombo-inflammatory prognostic score (TIPS) and BISAP.